Targeted Thrombolysis with Magnetic Nanotherapeutics: A Translational Assessment.

Plasminogen activators, such as recombinant tissue-type plasminogen activators (rtPAs), while effective in treating thromboembolic diseases, often induce hemorrhagic complications due to non-specific enzyme activities in the systemic circulation. This study evaluated the targeting efficiency, efficacy, biodistribution, and potential toxicity of a rtPA covalently attached to chitosan-coated magnetic nanoparticles (chitosan-MNP-rtPA). The thrombolytic activity of a chitosan-MNP-rtPA was preserved by protection from an endogenous plasminogen activator inhibitor-1 (PAI-1) in whole blood and after circulation in vivo, as examined by thromboelastometry. Single-photon emission computed tomography (SPECT) demonstrated real-time retention of a 99mTc-MNP-rtPA induced by magnet application in a rat embolic model; an 80% reduction in rtPA dosage for a chitosan-MNP-rtPA with magnetic guidance was shown to restore blood flow. After treatment, iron deposition was observed in the reticuloendothelial systems, with portal edema and neutrophil infiltration in the liver at a ten-fold higher dose but not the regular dose. Nevertheless, no liver or renal toxicity was observed at this higher dose. In conclusion, the liver may still be the major deposit site of rtPA nanocomposites after targeted delivery; chitosan-coated MNPs are potentially amenable to target therapeutics with parenteral administration.

Dietary Selenium Insufficiency Induces Cardiac Inflammatory Injury in Chicks.

BACKGROUND: Laying hens undergo intensive metabolism and are vulnerable to cardiac insults. Previous research demonstrated overt heart disorders of broiler chickens induced by dietary Se deficiency. OBJECTIVES: This study aimed to reveal effects and mechanism of dietary Se insufficiency on cardiac injuries of egg-type chicks in their early life. METHODS: White Leghorn chicks (0-d-old, female) were fed a corn-soy, Se-insufficient basal diet (BD, 0.05 mg Se/kg; n = 11) or the BD supplemented with 0.3 mg Se/kg (as sodium selenite; n = 8) for 35 d. Cardiac tissues were collected at the end of study for histology and to determine its relationship with heart Se contents, selenoprotein expression profiles, antioxidant and inflammatory status, and the Toll-like receptor 4/extracellular signal-regulated kinases/p38 map kinase/c-Jun N-terminal kinase (TLR4/ERK/P38/JNK) pathway. RESULTS: Compared with those fed 0.35 mg Se/kg, chicks fed BD had significantly lower body weights and average daily gain, and 28% lower heart Se, and developed cardiac mononuclear inflammatory cell infiltration, along with elevated (P < 0.05) serum concentrations of creatine kinase, aldolase, and interleukin-1 (IL-1). The BD decreased (P < 0.05) body weight and heart glutathione contents and expression of selenoproteins but increased (P < 0.05) heart concentrations of malondialdehyde and reactive oxygen species. These changes were associated with increased (P < 0.05) mRNA and/or protein concentrations of cyclooxygenases, lipoxygenase-12, cytokines (IL-1ß), nuclear factor (NF) κB subunit, chemokines, and receptors (CCL20, CXCR1, and CXCLI2) and increased (P < 0.1) TLR4/ERK /P38/JNK in the heart of Se-insufficient chicks. CONCLUSIONS: Dietary Se insufficiency induces infiltration of mononuclear inflammatory cells in the heart of egg-type chicks. This cardiac injury was mediated by decreased functional expressions of selenoproteins, which resulted in apparent elevated oxidative stress and subsequent activations of the TLR4 pathway and NF κB.

Research Progress on Active Ingredients and Product Development of Lycium ruthenicum Murray.

Lycium ruthenicum Murray possesses significant applications in both food and medicine, including antioxidative, anti-tumor, anti-fatigue, anti-inflammatory, and various other effects. Consequently, there has been a surge in research endeavors dedicated to exploring its potential benefits, necessitating the organization and synthesis of these findings. This article systematically reviews the extraction and content determination methods of active substances such as polysaccharides, anthocyanins, flavonoids, and polyphenols in LRM in the past five years, as well as some active ingredient composition determination methods, biological activities, and product development. This review is divided into three main parts: extraction and determination methods, their bioactivity, and product development. Building upon prior research, we also delve into the economic and medicinal value of Lycium ruthenicum Murray, thereby contributing significantly to its further exploration and development. It is anticipated that this comprehensive review will serve as a valuable resource for advancing research on Lycium ruthenicum Murray.

Cpd-A1 alleviates acute kidney injury by inhibiting ferroptosis.

Acute kidney injury (AKI) is defined as sudden loss of renal function characterized by increased serum creatinine levels and reduced urinary output with a duration of 7 days. Ferroptosis, an iron-dependent regulated necrotic pathway, has been implicated in the progression of AKI, while ferrostatin-1 (Fer-1), a selective inhibitor of ferroptosis, inhibited renal damage, oxidative stress and tubular cell death in AKI mouse models. However, the clinical translation of Fer-1 is limited due to its lack of efficacy and metabolic instability. In this study we designed and synthesized four Fer-1 analogs (Cpd-A1, Cpd-B1, Cpd-B2, Cpd-B3) with superior plasma stability, and evaluated their therapeutic potential in the treatment of AKI. Compared with Fer-1, all the four analogs displayed a higher distribution in mouse renal tissue in a pharmacokinetic assay and a more effective ferroptosis inhibition in erastin-treated mouse tubular epithelial cells (mTECs) with Cpd-A1 (N-methyl-substituted-tetrazole-Fer-1 analog) being the most efficacious one. In hypoxia/reoxygenation (H/R)- or LPS-treated mTECs, treatment with Cpd-A1 (0.25 µM) effectively attenuated cell damage, reduced inflammatory responses, and inhibited ferroptosis. In ischemia/reperfusion (I/R)- or cecal ligation and puncture (CLP)-induced AKI mouse models, pre-injection of Cpd-A1 (1.25, 2.5, 5 mg·kg-1·d-1, i.p.) dose-dependently improved kidney function, mitigated renal tubular injury, and abrogated inflammation. We conclude that Cpd-A1 may serve as a promising therapeutic agent for the treatment of AKI.

PRRX1 upregulates PD-L1 in human mesenchymal stem cells.

Mesenchymal stem cells (MSCs) have been demonstrated to be efficacious in clinical applications for the amelioration of immune disorders, including graft-versus-host disease (GvHD) and Crohn's disease. The immunosuppressive role of Programmed death-ligand 1 (PD-L1) in MSCs is pivotal, yet the regulatory mechanisms governing its expression remain to be fully elucidated. In this study, we explored the influence of paired-related homeobox (PRRX1), a determinant of multipotency and self-renewal in MSCs, on the expression of various surface antigens, notably PD-L1. Multiple isoforms of PRRX1 were found to augment the mRNA levels of MSC markers, such as CD26 and CD317, with all isoforms elevating PD-L1 expression at both mRNA and protein levels. This study reveals that PRRX1 may act as a potential immunomodulatory factor in MSCs by regulating the PD-L1 pathway.

Development and evaluation of ultrasound image tracking technology based on Mask R-CNN applied to respiratory motion compensation system.

Background: For respiration induced tumor displacement during a radiation therapy, a common method to prevent the extra radiation is image-guided radiation therapy. Moreover, mask region-based convolutional neural networks (Mask R-CNN) is one of the state-of-the-art (SOTA) object detection frameworks capable of conducting object classification, localization, and pixel-level instance segmentation. Methods: We developed a novel ultrasound image tracking technology based on Mask R-CNN for stable tracking of the detected diaphragm motion and applied to the respiratory motion compensation system (RMCS). For training Mask R-CNN, 1800 ultrasonic images of the human diaphragm are collected. Subsequently, an ultrasonic image tracking algorithm was developed to compute the mean pixel coordinates of the diaphragm detected by Mask R-CNN. These calculated coordinates are then utilized by the RMCS for compensation purposes. The tracking similarity verification experiment of mask ultrasonic imaging tracking algorithm (M-UITA) is performed. Results: The correlation between the input signal and the signal tracked by M-UITA was evaluated during the experiment. The average discrete Fréchet distance was less than 4 mm. Subsequently, a respiratory displacement compensation experiment was conducted. The proposed method was compared to UITA, and the compensation rates of three different respiratory signals were calculated and compared. The experimental results showed that the proposed method achieved a 6.22% improvement in compensation rate compared to UITA. Conclusions: This study introduces a novel method called M-UITA, which offers high tracking precision and excellent stability for monitoring diaphragm movement. Additionally, it eliminates the need for manual parameter adjustments during operation, which is an added advantage.

[Characterization of Microplastic Leachate from Different Polymers and Its Effect on Seed Germination of Lettuce].

Accumulation of microplastics in soil could interfere with the germination and growth of plants. However, the chemical risks raised by leachate of microplastics remain unknown. Here, we prepared microplastic leachate at different extraction temperatures (25 and 50℃) using microplastic fibers derived from polyamide (PA) and polyethylene (PE) and conducted the seed germination test of microplastic leachates to investigate the toxic effects of microplastic leachates on lettuce (Lactuca sativa L.). Furthermore, characteristics of the microplastic leachate, such as DOC and DON concentrations and parameters of UV-vis, were measured. The results revealed that the concentration of DOC and DON in the leachate of PA was significantly higher than that of PE. DOC and DON concentration in the leachate of PA increased with extraction temperature. Additionally, the aromaticity, hydrophobic component content, and molecular weight of leachates were significantly affected by the polymers of microplastic, whereas the extraction temperature had no effect. Compared to those in CK, the microplastic leachates reduced the indicators such as germination vigor, germination index, and vigor index of lettuce seeds; however, it had no impact on agronomic traits, such as plant height, root length, fresh weight, and dry weight. Meanwhile, some seeds had abnormal developments of radicles and cotyledons under the microplastic leachate treatments. This demonstrates that the substances leached from microplastics could interfere with the germination process of lettuce seeds. Therefore, the chemical risks exerted by the microplastics to the soil and plant system require further attention.

Cognitive engagement of nursing undergraduates in blended learning: A parallel mixed method study.

BACKGROUND: Blended learning is being integrated into undergraduate nursing education at all levels and from all directions. Cognitive engagement is not only an embodiment and guarantee of students' engagement into the curriculum from a cognitive level, deep engagement and high-level thinking, but also an important indicator of whether students are effectively engaged in the blended learning curricula. However, no studies have been seen to investigate the cognitive engagement of nursing undergraduates in the blended learning curricula and its influential factors. OBJECTIVES: To explore nursing undergraduates' cognitive engagement during the blended learning curricula and its influential factors. DESIGN: A convergent parallel mixed-methods was used. Data were collected between November 2021 and May 2022, inclusive. SETTINGS AND PARTICIPANTS: The study was carried out in the nursing school at a university in China. Participants including students undertaking entry to the blended learning curricula. METHODS: In the quantitative component (n = 142), participants' cognitive engagement was investigated and factors associated with it were examined using univariate analysis, correlation analysis and multiple regression analysis. During this period, personal, semi-structured interviews were conducted with a subset of these participants (n = 15) to understand participants' cognitive engagement experiences. RESULTS: The cognitive engagement of nursing undergraduates was at a moderate level and the cognitive engagement experiences were reflected in the four themes of Reconstitution, Connection, Elaboration and Retention. The influential factors of cognitive engagement were learning activities (ß = 0.226, p = 0.004), autonomy (ß = 0.158, p = 0.047), academic self-efficacy (ß = 0.311, p < 0.001, ß = 0.271, p < 0.001) and social interaction (ß = 0.358, p < 0.001). CONCLUSIONS: The cognitive engagement of nursing undergraduates in the blended learning curricula needs to be improved. To maximize promote cognitive engagement of nursing undergraduates in the blended learning curricula, educators should design diverse learning activities, engage in high quality social interactions with students, and maximize students' autonomy and self-efficacy.

N6-methyladenosine-modified circIRF2, identified by YTHDF2, suppresses liver fibrosis via facilitating FOXO3 nuclear translocation.

Circular RNA (circRNA) has been implicated in liver fibrosis and modulated by multiple elusive molecular mechanisms, while the effects of N6-methyladenosine (m6A) modification on circRNA are still elusive. Herein, we identify circIRF2 from our circRNA sequencing data, which decreased in liver fibrogenesis stage and restored in resolution stage, indicating that dysregulated circIRF2 may be closely associated with liver fibrosis. Gain/loss-of-function analysis was performed to evaluate the effects of circIRF2 on liver fibrosis at both the fibrogenesis and resolution in vivo. Ectopic expression of circIRF2 attenuated liver fibrogenesis and HSCs activation at the fibrogenesis stage, whereas downregulation of circIRF2 impaired mouse liver injury repair and inflammation resolution. Mechanistically, YTHDF2 recognized m6A-modified circIRF2 and diminished circIRF2 stability, partly accounting for the decreased circIRF2 in liver fibrosis. Microarray was applied to investigate miRNAs regulated by circIRF2, our data elucidate cytoplasmic circIRF2 may directly harbor miR-29b-1-5p and competitively relieve its inhibitory effect on FOXO3, inducing FOXO3 nuclear translocation and accumulation. Clinically, circIRF2 downregulation was prevalent in liver fibrosis patients compared with healthy individuals. In summary, our findings offer a novel insight into m6A modification-mediated regulation of circRNA and suggest that circIRF2 may be an exploitable prognostic marker and/or therapeutic target for liver fibrosis.

DNAJ heat shock protein family member C1 can regulate proliferation and migration in hepatocellular carcinoma.

Background: DNAJ heat shock protein family (Hsp40) member C1(DNAJC1) is a member of the DNAJ family. Some members of the DNAJ gene family had oncogenic properties in many cancers. However, the role of DNAJC1 in hepatocellular carcinoma (HCC) was unclear. Methods: In this study, expression and prognostic value of DNAJC1 in HCC were analyzed by bioinformatics. Quantitative real-time PCR and Western blotting were used to verify DNAJC1 expression in liver cancer cell lines. Furthermore, immunohistochemical (IHC) was used to detect DNAJC1 expression in liver cancer tissues. Subsequently, the effect of DNAJC1 on the proliferation, migration, invasion and apoptosis of HCC cells was detected by knocking down DNAJC1. Finally, gene set enrichment analysis (GSEA) was used to investigate the potential mechanism of DNAJC1 and was verified by Western blotting. Results: DNAJC1 was highly expressed in HCC and was significantly associated with the prognosis of patients with HCC. Importantly, the proliferation, migration and invasion of Huh7 and MHCC97H cells were inhibited by the knockdown of DNAJC1 and the knockdown of DNAJC1 promoted Huh7 and MHCC97H cell apoptosis. Furthermore, compared to the negative control group, DNAJC1 knockdown in Huh7 and MHCC97H cells promoted the expression of p21, p53, p-p53(Ser20), Bax and E-cadherin proteins, while inhibiting the expression of PARP, MMP9, Vimentin, Snai1, Bcl-2 and N-cadherin proteins. Conclusions: DNAJC1 had a predictive value for the prognosis of HCC. Knockdown of DNAJC1 may inhibit HCC cell proliferation, migration and invasion and promote the HCC cell apoptosis through p53 and EMT signaling pathways.

IPAC integrates rewarding and environmental memory during the acquisition of morphine CPP.

The association between rewarding and drug-related memory is a leading factor for the formation of addiction, yet the neural circuits underlying the association remain unclear. Here, we showed that the interstitial nucleus of the posterior limb of the anterior commissure (IPAC) integrated rewarding and environmental memory information by two different receiving projections from ventral tegmental area (VTA) and nucleus accumbens shell region (NAcSh) to mediate the acquisition of morphine conditioned place preference (CPP). A projection from the VTA GABAergic neurons (VTAGABA) to the IPAC lateral region GABAergic neurons (IPACLGABA) mediated the effect of morphine rewarding, whereas the pathway from NAcSh dopamine receptor 1-expressing neurons (NAcShD1) to the IPAC medial region GABAergic neurons (IPACMGABA) was involved in the acquisition of environmental memory. These findings demonstrated that the distinct IPAC circuits VTAGABA→IPACLGABA and NAcShD1R→IPACMGABA were attributable to the rewarding and environmental memory during the acquisition of morphine CPP, respectively, and provided the circuit-based potential targets for preventing and treating opioid addiction.

Heterointerface construction for permalloy microparticles through the surface modification of bilayer metallic organic frameworks: Toward microwave absorption enhancement.

Reasonable heterointerface modification can effectively regulate and enhance the microwave absorption of electromagnetic materials. The surface of magnetic permalloy (PM) microparticles is modified herein by coating double-layer metal organic frameworks (MOF), which are composed of a 2-methylimidazole cobalt salt (ZIF-67) layer and a 2-methylimidazole zinc salt (ZIF-8) layer. A stable heterointerface structure with cobalt/carbon (Co/C) and zinc/carbon (Zn/C) layers is formed on the surface of PM microparticles after pyrolysis. These particles include two types of composite particles of PM solely encapsulated by ZIF-67 or ZIF-8, PM@ZIF67 and PM@ZIF8, respectively, and two types of composite PM particles with a double-layered MOF outer shell structure obtained by exchanging the coating sequence (PM@ZIF8@ZIF67 and PM@ZIF67@ZIF8). Furthermore, the thermal decomposition temperature has a significant impact on the surface morphology and magnetic properties of the composite particles. After pyrolyzing at 500 °C, the PM@ZIF67@ZIF8 samples exhibit the highest microwave absorption performance among these samples. Specifically, the minimum reflection loss and effective absorption bandwidth of PM@ZIF67@ZIF8 after pyrolyzing at 500 °C can reach -47.3 dB at a matching thickness of 3.8 mm and 5.3 GHz at a matching thickness of 2.5 mm, respectively. A heterointerface with an electrical field orientation is created in the PM@ZIF67@ZIF8 particles, which effectively enhances the interface polarization and dipole polarization. Furthermore, the formation of a three-dimensional carbon network after pyrolysis is also useful for optimizing impedance matching and enhancing magneto-electric synergism.

Compound-42 alleviates acute kidney injury by targeting RIPK3-mediated necroptosis.

BACKGROUND AND PURPOSE: Necroptosis plays an essential role in acute kidney injury and is mediated by receptor-interacting protein kinase 1 (RIPK1), receptor-interacting protein kinase 3 (RIPK3), and mixed lineage kinase domain-like pseudokinase (MLKL). A novel RIPK3 inhibitor, compound 42 (Cpd-42) alleviates the systemic inflammatory response. The current study was designed to investigate whether Cpd-42 exhibits protective effects on acute kidney injury and reveal the underlying mechanisms. EXPERIMENTAL APPROACH: The effects of Cpd-42 were determined in vivo through cisplatin- and ischaemia/reperfusion (I/R)-induced acute kidney injury and in vitro through cisplatin- and hypoxia/re-oxygenation (H/R)-induced cell damage. Transmission electron microscopy and periodic acid-Schiff staining were used to identify renal pathology. Cellular thermal shift assay and RIPK3-knockout mouse renal tubule epithelial cells were used to explore the relationship between Cpd-42 and RIPK3. Molecular docking and site-directed mutagenesis were used to determine the binding site of RIPK3 with Cpd-42. KEY RESULTS: Cpd-42 reduced human proximal tubule epithelial cell line (HK-2) cell damage, necroptosis and inflammatory responses in vitro. Furthermore, in vivo, cisplatin- and I/R-induced acute kidney injury was alleviated by Cpd-42 treatment. Cpd-42 inhibited necroptosis by interacting with two key hydrogen bonds of RIPK3 at Thr94 and Ser146, which further blocked the phosphorylation of RIPK3 and mitigated acute kidney injury. CONCLUSION AND IMPLICATIONS: Acting as a novel RIPK3 inhibitor, Cpd-42 reduced kidney damage, inflammatory response and necroptosis in acute kidney injury by binding to sites Thr94 and Ser146 on RIPK3. Cpd-42 could be a promising treatment for acute kidney injury.

Identification and characterization of a Reeler domain containing protein in Procambarus clarkii provides new insights into antibacterial immunity in crustacean.

Crayfish, as an invertebrate, relies only on the innate immune system to resist external pathogens. In this study, a molecule containing a single Reeler domain was identified from red swamp crayfish Procambarus clarkii (named as PcReeler). Tissue distribution analysis showed that PcReeler was highly expressed in gills and its expression was induced by bacterial stimulation. Inhibiting the expression of PcReeler by RNA interference led to a significant increase in the bacterial abundance in the gills of crayfish, and a significant increase in the crayfish mortality. Silencing of PcReeler influenced the stability of the microbiota in the gills revealed by 16S rDNA high-throughput sequencing. Recombinant PcReeler showed the ability to bind microbial polysaccharide and bacteria and to inhibit the formation of bacterial biofilms. These results provided direct evidence for the involvement of PcReeler in the antibacterial immune mechanism of P. clarkii.

Airway morphological abnormalities of bronchiolitis assessed by endobronchial optical coherence tomography.

BACKGROUND: A few studies have reported the medium-sized and small airway morphological abnormalities of bronchiolitis. Whether spirometry or impulse oscillometry (IOS) is correlated with airway remodeling of bronchiolitis remains unclear. OBJECTIVES: Aiming to demonstrate the airway morphological abnormalities of bronchiolitis obliterans (BO) and diffuse panbronchiolitis (DPB) assessed by endobronchial optical coherence tomography (EB-OCT), and elucidate whether spirometric and IOS parameters have correlation with the airway remodeling of bronchiolitis. METHODS: We recruited 18 patients with bronchiolitis (BO, n = 9; DPB, n = 9) and 17 control subjects. Assessments of clinical features, St. George's respiratory questionnaire (SGRQ), chest computed tomography (CT), spirometry, IOS, and EB-OCT were performed in all enrolled subjects. The correlation between EB-OCT and lung function parameters was studied and analyzed. RESULTS: The magnitude of abnormalities of spirometric and IOS parameters was significantly greater in patients with bronchiolitis than that in control subjects (p < 0.05). Patients with BO had notably lower forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, maximal mid-expiratory flow (MMEF)% pred and higher resonant frequency (Fres), and area of reactance (AX) than those with DPB (p < 0.05). The EB-OCT measurement among patients with bronchiolitis and between the bronchus in the left and the right lung demonstrated a heterogeneous distribution of airway calibers, presenting a high intra- and inter-individual variability. Patients with bronchiolitis had notably greater airway wall area (p < 0.05) compared with control, while BO presented greater magnitude of airway abnormalities than DPB. Fres and the difference in airway resistance at 5 and 20 Hz (R5-R20) correlated negatively with medium-sized and small airway inner area, and correlated positively with airway wall area (p < 0.05), whose correlation coefficients were higher than those of spirometric parameters. CONCLUSION: Bronchiolitis, BO and DPB, manifested a heterogeneous distribution of airway calibers with significant intra- and inter-individual variability. IOS parameters, rather than spirometry, correlated better with medium-sized and small airway remodeling in bronchiolitis assessed by EB-OCT measurement.

Population pharmacokinetics and dosing regimen optimization of levetiracetam in epilepsy during pregnancy.

AIMS: The pharmacokinetics of levetiracetam (LEV) significantly changed during pregnancy. It is a great challenge to predict the adjusted doses of LEV to reach the preconception target concentrations. This study aimed to establish a population pharmacokinetic model of LEV in women with epilepsy (WWE) during pregnancy to analyse the factors of pharmacokinetic variability and to develop a model-based individualized dosing regimen. METHODS: A total of 166 concentration-time points from 37 WWE during pregnancy treated with LEV were collected to analyse LEV pharmacokinetics with nonlinear mixed-effects modelling. The dosing regimen was optimized by Monte Carlo simulations based on the final model. RESULTS: The LEV pharmacokinetics in pregnant WWE were best described by a 1-compartment model of first-order absorption and elimination. The population typical value of apparent clearance (CL/F) in the final model was estimated to be 3.82 L/h (95% confidence interval 3.283-4.357 L/h) with a relative standard error of 7.2%. Both total body weight (TBW) and trimester of pregnancy were significantly associated with LEV-CL/F during pregnancy; LEV-CL/F increased by 42.72% when TBW increased from 55 to 65 kg from the first trimester to the second trimester. Monte Carlo simulations showed that dosing regimens for LEV should be individualized based on the patient's TBW and trimester of pregnancy to maximize the likelihood of achieving the therapeutic range. CONCLUSION: This first population pharmacokinetic study of LEV in WWE during pregnancy supports the use of a weight-based and pregnancy-based dosing regimen and can lay a foundation for further optimizing the individualized dosing regimens.

The effectiveness of auricular acupressure on pain management during labor: A systematic review and meta-analysis of randomized controlled trials.

AIM: This meta-analysis aimed to systematically evaluate the effectiveness of auricular acupressure on pain management during labor. METHODS: Six English and three Chinese electronic databases were comprehensively searched from inception to 6 November 2021. The PRISMA checklist was followed. The methodological quality of the included studies was assessed with the Cochrane Collaboration Bias Risk Assessment Tool. The meta-analysis was performed using Review Manager 5.3 software. Heterogeneity between studies was calculated using I2 . RESULTS: Five studies comprising 312 participants were included. The labor pain scores of the auricular acupressure group were significantly lower than those of the usual care group at cervix dilations of 6, 8, and 10 cm, with mean differences (95% confidence intervals) of -1.05 (-1.41, -0.69), -1.44 (-2.07, -0.82), and -1.96 (-3.30, -0.61), respectively. Auricular acupressure can thus effectively improve the labor pain perception at cervix dilations of 6, 8, and 10 cm. Moreover, auricular acupressure shortened the active phase, and had the trend of shortening the second and third stages of labor. There was no evidence that auricular acupressure had an effect on the rate of cesarean section or the 1 and 5 min Apgar scores. CONCLUSION: Effective labor pain relief, better labor pain perception, and the lack of adverse effects support the use of auricular acupressure. More high-quality and rigorous trials are needed to verify our findings before we can make strong recommendations.

Comparison of aspirin treatment strategies for primary prevention of cardiovascular diseases: A decision-analytic Markov modelling study / 北京大学学报(医学版)

OBJECTIVE@#To compare the expected population impact of benefit and risk of aspirin treatment strategies for the primary prevention of cardiovascular diseases recommended by different guidelines in the Chinese Electronic Health Records Research in Yinzhou (CHERRY) study.@*METHODS@#A decision-analytic Markov model was used to simulate and compare different strategies of aspirin treatment, including: Strategy ①: Aspirin treatment for Chinese adults aged 40-69 years with a high 10-year cardiovascular risk, recommended by the 2020 Chinese Guideline on the Primary Prevention of Cardiovascular Diseases; Strategy ②: Aspirin treatment for Chinese adults aged 40-59 years with a high 10-year cardiovascular risk, recommended by the 2022 United States Preventive Services Task Force Recommendation Statement on Aspirin Use to Prevent Cardiovascular Disease; Strategy ③: Aspirin treatment for Chinese adults aged 40-69 years with a high 10-year cardiovascular risk and blood pressure well-controlled (< 150/90 mmHg), recommended by the 2019 Guideline on the Assessment and Management of Cardio-vascular Risk in China. The high 10-year cardiovascular risk was defined as the 10-year predicted risk over 10% based on the 2019 World Health Organization non-laboratory model. The Markov model simulated different strategies for ten years (cycles) with parameters mainly from the CHERRY study or published literature. Quality-adjusted life year (QALY) and the number needed to treat (NNT) for each ischemic event (including myocardial infarction and ischemic stroke) were calculated to assess the effectiveness of the different strategies. The number needed to harm (NNH) for each bleeding event (including hemorrhagic stroke and gastrointestinal bleeding) was calculated to assess the safety. The NNT for each net benefit (i.e., the difference of the number of ischemic events could be prevented and the number of bleeding events would be added) was also calculated. One-way sensitivity analysis on the uncertainty of the incidence rate of cardiovascular diseases and probabilistic sensitivity analysis on the uncertainty of hazard ratios of interventions were conducted.@*RESULTS@#A total of 212 153 Chinese adults, were included in this study. The number of people who were recommended for aspirin treatment Strategies ①-③ was 34 235, 2 813, and 25 111, respectively. The Strategy ③ could gain the most QALY of 403 [95% uncertainty interval (UI): 222-511] years. Compared with Strategy ①, Strategy ③ had similar efficiency but better safety, with the extra NNT of 4 (95%UI: 3-4) and NNH of 39 (95%UI: 19-132). The NNT per net benefit was 131 (95%UI: 102-239) for Strategy ①, 256 (95%UI: 181-737) for Strategy ②, and 132 (95%UI: 104-232) for Strategy ③, making Strategy ③ the most favorable option with a better QALY and safety, along with similar efficiency in terms of net benefit. The results were consistent in the sensitivity analyses.@*CONCLUSION@#The aspirin treatment strategies recommended by the updated guidelines on the primary prevention of cardiovascular diseases showed a net benefit for high-risk Chinese adults from developed areas. However, to balance effectiveness and safety, aspirin is suggested to be used for primary prevention of cardiovascular diseases with consideration for blood pressure control, resulting in better intervention efficiency.

Effect of Baicalin on Pyroptosis of Diffuse Large B-Cell Lymphoma Cell Lines DB and Its Mechanism / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of Baicalin on the proliferation and pyroptosis of diffuse large B-cell lymphoma cell line DB and its mechanism.@*METHODS@#DB cells were treated with baicalin at different concentrations (0, 5, 10, 20, 40 μmol/L). Cell proliferation was detected by CCK-8 assay and half maximal inhibitory concentration (IC50) was calculated. The morphology of pyroptosis was observed under an inverted microscope, the integrity of the cell membrane was verified by LDH content release assay, and the expressions of pyroptosis-related mRNA and protein (NLRP3, GSDMD, GSDME, N-GSDMD, N-GSDME) were detected by real-time fluorescence quantitative PCR and Western blot. In order to further clarify the relationship between baicalin-induced pyroptosis and ROS production in DB cells, DB cells were divided into control group, baicalin group, NAC group and NAC combined with baicalin group. DB cells in the NAC group were pretreated with ROS inhibitor N-acetylcysteine (NAC) 2 mmol/L for 2 h. Baicalin was added to the combined treatment group after pretreatment, and the content of reactive oxygen species (ROS) in the cells was detected by DCFH-DA method after 48 hours of culture.@*RESULTS@#Baicalin inhibited the proliferation of DB cells in a dose-dependent manner (r=-0.99), and the IC50 was 20.56 μmol/L at 48 h. The morphological changes of pyroptosis in DB cells were observed under inverted microscope. Compared with the control group, the release of LDH in the baicalin group was significantly increased (P<0.01), indicating the loss of cell membrane integrity. Baicalin dose-dependently increased the expression levels of NLRP3, N-GSDMD, and N-GSDME mRNA and protein in the pyroptosis pathway (P<0.05). Compared with the control group, the level of ROS in the baicalin group was significantly increased (P<0.05), and the content of ROS in the NAC group was significantly decreased (P<0.05). Compared with the NAC group, the content of ROS in the NAC + baicalin group was increased. Baicalin significantly attenuated the inhibitory effect of NAC on ROS production (P<0.05). Similarly, Western blot results showed that compared with the control group, the expression levels of pyroptosis-related proteins was increased in the baicalin group (P<0.05). NAC inhibited the expression of NLRP3 and reduced the cleavage of N-GSDMD and N-GSDME (P<0.05). Compared with the NAC group, the NAC + baicalin group had significantly increased expression of pyroptosis-related proteins. These results indicate that baicalin can effectively induce pyroptosis in DB cells and reverse the inhibitory effect of NAC on ROS production.@*CONCLUSION@#Baicalin can inhibit the proliferation of DLBCL cell line DB, and its mechanism may be through regulating ROS production to affect the pyroptosis pathway.

Improving acupuncture research: progress, guidance, and future directions / 中国针灸

This paper makes an interpretation of the collection Acupuncture: how to improve the evidence base published by BMJ & BMJ Open. Studies show that the quality of randomized controlled trial (RCT) of acupuncture is low, and multivariable Meta-regression analysis fails to confirm most factors commonly believed to influence the effect of acupuncture. The methodological challenges in design and conduct of RCT in acupuncture were analyzed, and a consensus on how to design high-quality acupuncture RCT was developed. The number of acupuncture systematic reviews was huge but the evidence was underused in clinical practice and health policy, and a large number of western clinical practice guidelines recommended acupuncture therapy, but the usefulness of recommendations needed to be improved. In view of the problems in clinical research on acupuncture mentioned in this collection, combined with the analysis of the purpose of clinical research on acupuncture, perspectives, study types, as well as the relationship between evidence and clinical decision-making, a five-stage study paradigm of clinical research on acupuncture is proposed.